Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT00782275|
Recruitment Status : Completed
First Posted : October 31, 2008
Results First Posted : December 20, 2017
Last Update Posted : January 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma Kidney Cancer||Drug: bevacizumab Drug: temsirolimus||Phase 2|
Avastin, a humanized IgG1 monoclonal antibody (MAb), inhibits vascular endothelial growth factor (VEGF). VEGF is one of the most potent and specific proangiogenic factors and has been identified as a crucial regulator of both normal and pathological angiogenesis. Temsirolimus specifically inhibits the mammalian target of rapamycin (mTOR), a highly conserved serine/threonine kinase which regulates cell growth and metabolism in response to environmental factors. The combination avastin and temsirolimus has already demonstrated efficacy in the phase I setting
The primary endpoint is 4-month PFS. The null and alternative hypotheses are 50% vs. 70%. Assuming 2 ineligible patients, the target sample size is 41 patients (39 eligible patients). The probability of concluding that the treatment is effective was >0.90 if the true rate is at least 70%. The probability of concluding that the treatment is effective was ≤ 0.10 if the true rate was 50% or less. If 24 or more patients are alive and progression-free at 4 months, then this regimen would be considered for further study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma|
|Actual Study Start Date :||April 2009|
|Primary Completion Date :||May 2015|
|Study Completion Date :||May 2015|
Experimental: bevacizumab and temsirolimus
bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15)
temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22
There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.
Other Name: avastinDrug: temsirolimus
Other Name: torisel
- 4-month Progression-Free Survival Rate [ Time Frame: Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment. Relevant for this endpoint was disease status at 4 months. ]4-month progression-free survival rate was defined as the percentage of participants absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
- Objective Response Rate [ Time Frame: Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment; Treatment continued until disease progression or unacceptable toxicity. Median (range) of treatment duration for this study cohort was 5 cycles (1-39) [1 cycle=28days]. ]Objective response (OR) rate is the percentage of participants achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
- Overall Survival [ Time Frame: Median follow-up for survival in this study cohort is 56 months. ]Overall survival (OS) is defined from the date of registration to date of death, or censored at the date the participant was last known alive. OS is estimated based on the Kaplan-Meier method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00782275
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02115|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Tennessee|
|Vanderbilt Univeristy Medical Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||David McDermott, MD||Beth Israel Deaconess Medical Center|